Spatiotemporally Targeted Nanomedicine Overcomes Hypoxia-Induced Drug Resistance of Tumor Cells after Disrupting Neovasculature

• DOI: 10.1021/acs.nanolett.0c02515
• Publication Date: 2020-07-22T20:19:22Z
• Authors: Jinjin Chen; Zhongyu Jiang; Weiguo Xu; Tianmeng Sun; Xiuli Zhuang; Jianxun Ding; Xuesi Chen
• Keywords: Hypoxia; Combretastatin; Tumor Hypoxia; Targeted drug delivery

Vascular disrupting agents (VDAs) are emerging anticancer agents, which show rising demand for combination with cytostatic drugs (CSDs), owing to inadequate tumor inhibition when applied singly. Nevertheless, the remains a challenge due different working sites of VDAs and CSDs hypoxia-induced drug resistance after neovasculature by VDAs. Herein, we developed shell-stacked nanoparticle (SNP) coencapsulation VDA combretastatin A-4 phosphate (CA4P) proteasome inhibitor bortezomib (BTZ). The SNP could spatiotemporally deliver CA4P BTZ cells mediated site-specific stimuli-activated release. Moreover, also reversed caused overexpressed ABCG2 under CA4P-induced hypoxic conditions. targeted therapy significantly inhibited growth both human A549 pulmonary adenocarcinoma xenograft model patient-derived (PDX) colon cancer in mice, providing promising strategy treating advanced cancers.